Aldehyde Dehydrogenases and Prostate Cancer: Shedding Light on Isoform Distribution to Reveal Druggable Target

Prostate cancer represents the most common malignancy diagnosed in men, and is the second-leading cause of cancer death in this population. In spite of dedicated efforts, the current therapies are rarely curative, requiring the development of novel approaches based on innovative molecular targets. In this work, we validated aldehyde dehydrogenase 1A1 and 1A3 isoform expressions in different prostatic tissue-derived cell lines (normal, benign and malignant) and patient-derived primary prostate tumor epithelial cells, demonstrating their potential for therapeutic intervention using a small library of aldehyde dehydrogenase inhibitors. Compound 3b, 6-(4-fluorophenyl)-2-phenylimidazo [1,2-a]pyridine exhibited not only antiproliferative activity in the nanomolar range against the P4E6 cell line, derived from localized prostate cancer, and PC3 cell lines, derived from prostate cancer bone metastasis, but also inhibitory efficacy against PC3 colony-forming efficiency. Considering its concomitant reduced activity against normal prostate cells, 3b has the potential as a lead compound to treat prostate cancer by means of a still untapped molecular target.

The value of 18F-PSMA-1007 PET/CT in identifying non-metastatic high-risk prostate cancer

Background Clinical management decisions on prostate cancer (PCa) are often based on a determination of risk. 68Ga-prostate-specific membrane antigen (PSMA)-11-positron emission tomography (PET)/computer tomography (CT) is an attractive modality to assess biochemical recurrence of PCa, detect metastatic disease and stage of primary PCa, making it a promising strategy for risk stratification. However, due to some limitation of 68Ga-PSMA-11 the development of alternative tracers is of high interest. In this study, we aimed to investigate the value of 18F-PSMA-1007 in identifying non-metastatic high-risk PCa. Methods A total of 101 patients with primary non-metastatic PCa who underwent 18F-PSMA-1007 PET/CT were retrospectively analyzed. According to the European Association of Urology guidelines on PCa, patients were classified into intermediate-risk (IR) group or high-risk (HR) group. The maximum standardized uptake values (SUVmax) of the primary prostate tumor were measured on PET/CT images. The diagnostic performance of PET/CT for IR and HR PCa was calculated, and the relationship between the SUVmax of primary prostate tumor, prostate-specific antigen (PSA) level and Gleason score (GS) was analyzed. Results Of all 101 patients, 49 patients were classified into IR group and 52 patients were classified into HR group. There was a significant positive correlation between PSA level/GS and SUVmax (r = 0.561, r = 0.496, P < 0.001, respectively). Tumors with GS 6 and 7a showed significantly lower 18F-PSMA-1007 uptake compared to patients with GS 8 and 9 (P < 0.01). SUVmax in patients of HR was significantly higher than those of IR (median SUVmax: 16.85 vs 7.80; P < 0.001). In receiver operating characteristic curve analysis, the optimal cutoff value of the SUVmax for identifying high-risk PCa was set as 9.05 (area under the curve: 0.829; sensitivity: 90.4%; specificity: 65.3%). Conclusion 18F-PSMA-1007 PET/CT showed the powerful diagnosis efficacy for high-risk PCa, which can be used as an objective imaging reference index for clinical reference.

The Value of 18F-PSMA-1007 PET/CT in Identifying High-Risk Prostate Cancer

Background: Clinical management decisions on prostate cancer (PCa) are often based on a determination of risk. 68Ga-prostate-specific membrane antigen (PSMA)-11-positron-emission-tomography (PET)/ computer-tomography (CT) is an attractive modality to assess biochemical recurrence of PCa, detect metastatic disease and stage of primary PCa, making it a promising strategy for risk stratification. However, due to some limitation of 68Ga-PSMA-11 the development of alternative tracers is of high interest. In this study, we aimed to investigate the value of the new PET trace 18F-PSMA-1007 in identifying high-risk PCa.Methods: 170 patients with primary PCa underwent 18F-PSMA-1007 PET/CT were retrospectively analyzed. According to the European Association of Urology (EAU) guidelines on prostate cancer for PCa, patients were classified into low-intermediate-risk (LMR) group or high-risk (HR) group. The maximum standardized uptake values (SUVmax) of the primary prostate tumor was measured on PET/CT images. The diagnostic performance of PET/CT for LMR and HR PCa were calculated and the relationship between the SUVmax of primary prostate tumor, prostate-specific antigen (PSA) level and Gleason score (GS) were analyzed.Results: Of all 170 patients, 55 patients were classified into LMR group and 115 patients were classified into HR group. There was a significant positive correlation between the PSA level/GS and SUVmax (r = 0.597, r = 0.446, P < 0.001, respectively). Tumors with GS of 6 and 7a showed significantly lower 18F-PSMA-1007 uptake compared to patients with GS of 8, 9, and 10 (P < 0.001). SUVmax in patients of HR was significantly higher than those of LMR (median SUVmax: 20.20 versus 8.40; P < 0.001). In receiver operating characteristic (ROC) curve analysis, the optimal cutoff value of the SUVmax for identifying high-risk PCa was set as 10.78 (area under the curve [AUC]: 0.873; sensitivity: 90.4%; specificity: 69.1%). Conclusion: 18F-PSMA-1007 PET/CT showed the powerful diagnosis efficacy for high-risk PCa, which can be used as an objective imaging reference index for clinical reference.